Title:Remarkable Effects of a Rhenium(I)-diselenoether Drug on the Production of
Cathepsins B and S by Macrophages and their Polarizations
Volume: 29
Issue: 30
Author(s): Philippe Collery*, Didier Desmaële, Adhikesavan Harikrishnan and Vijay Veena*
Affiliation:
- Society for the Coordination of Therapeutic Researches, 20220 Algajola, France
- School of Allied Healthcare and Sciences, Jain University, Bangalore 560066,
India
Keywords:
Rhenium (Re), rhenium(I)-diselenoether (Re-diSe), macrophages, immune resistance, cysteine proteases, cancer.
Abstract:
Background/Objective: Tumor-associated macrophages (TAMs) produce an excessive amount of
cysteine proteases, and we aimed to study the effects of anticancer rhenium(I)-diselenoether (Re-diSe) on the
production of cathepsins B and S by macrophages. We investigated the effect of Re-diSe on lipopolysaccharides
(LPS) induced M1 macrophages, or by interleukin 6 (IL-6) induced M2 macrophages.
Methods: Non-stimulated or prestimulated murine Raw 264 or human THP-1 macrophages were exposed to
increasing concentrations of the drug (5, 10, 20, 50 and 100 μM) and viability was assayed by the MTT assay.
The amount of cysteine proteases was evaluated by ELISA tests, the number of M1 and M2 macrophages by
the expression of CD80 or CD206 biomarkers. The binding of Re-diSe with GSH as a model thiol-containing
protein was studied by mass spectrometry.
Results: A dose-dependent decrease in cathepsins B and S was observed in M1 macrophages. There was no
effect in non-stimulated cells. The drug induced a dramatic dose-dependent increase in M1 expression in both
cells, significantly decreased the M2 expression in Raw 264 and had no effect in non-stimulated macrophages.
The binding of the Re atom with the thiols was clearly demonstrated.
Conclusion: The increase in the number of M1 and a decrease in M2 macrophages treated by Re-diSe could
be related to the decrease in cysteine proteases upon binding of their thiol residues with the Re atom.
